Multiple sclerosis (MS) is a chronic immune mediated disease characterized by recurrent attacks of neurologic dysfunction due to damage to the central nervous system. An animal model of MS, experimental allergic encephalomyelitis (EAE), also shows similar neurologic damage caused by T cells which recognize a portion (amino acids 89-101) of myelin basic protein (MBP), a major constituent of the myelin sheath surrounding nerve cells. Recently, a peptide analog of MBP corresponding to the region 89- 101 has been found to interfere with antigen recognition by T cells involved in the pathogenicity of this disease. Moreover, this peptide was able to inhibit the development of EAE when co-administered with MBP. We propose to conduct additional analoging efforts to identify the minimal peptide necessary to inhibit these self-reactive T cells in a variety of in vitro and in vivo assays. Further modifications are planned using D- amino acid substitutions to prolong the half-life and enhance the therapeutic benefit of the drug. This approach may help to identify compounds which are orally active, lipophilic and capable of passing the blood-brain barrier, and may aid in our management of MS.